MODORAMA

MODORAMA integrates analysis of protein family diversity, homology modeling, and alignment refinement to support selection of modeling templates and transfer of structural and functional annotations.

Key Features:

• Sequence and Structural Analysis: Analyzes sequence and structure conservation among homologous proteins.
• Functional Annotations: Annotates ligand-, DNA-, and RNA-binding sites, secondary structure, intrinsic disorder regions, crystallographic resolution, and model quality scores derived from alignments with known homologous structures.
• Template Selection for Modeling: Assists selection of appropriate templates for comparative modeling when the query structure is unknown by integrating sequence, structure, and annotation data.
• Alignment Refinement: Facilitates inspection and modification of target–template and other sequence alignments within a biological context.
• Dynamic Recalculation of Alignment-dependent Metrics: Automatically updates multiple sequence alignments, conservation scores, secondary structure predictions, solvent accessibility values, and local quality scores for implied three-dimensional models upon alignment modifications.

Scientific Applications:

• Identification of Structural Variation: Detects structural variations among homologs, including different conformational states and ligand interactions.
• Functional Annotation Transfer: Transfers functional annotations across homologous proteins based on sequence and structural alignments.
• Template Selection for Comparative Modeling: Supports selection of modeling templates based on sequence and structure conservation and mapped annotations.
• Alignment Refinement to Improve Model Accuracy: Refines and validates sequence alignments and enhances homology model accuracy through recalculation of conservation, secondary structure, solvent accessibility, and local quality scores.

Methodology:

Accepts a protein sequence or structure as input, generates alignments with homologous proteins, annotates binding sites, secondary structure, disorder regions and crystallographic resolution, computes model quality scores, updates multiple sequence alignments and recomputes conservation scores, secondary structure predictions, solvent accessibility values and local quality scores upon alignment modification, and supports selection of templates for comparative model construction.